crossing96/oncoscreening huggingface dataset:
Gene-mediated therapy for BCG-unresponsive nonmuscle-invasive bladder cancer: mechanisms, clinical evidence, and practical implementation.	PURPOSE OF REVIEW: Gene therapy has emerged as an attractive bladder-sparing strategy for patients with high-risk, Bacillus Calmette-Guérin (BCG)-unresponsive nonmuscle-invasive bladder cancer (NMIBC), addressing a therapeutic gap for those ineligible for or declining radical cystectomy. This review aims to describe the recent advances in gene-mediated therapies for BCG-unresponsive NMIBC. RECENT FINDINGS: The bladder's unique anatomy with direct intravesical access and capacity for high local exposure with minimal systemic absorption provides an ideal context for gene delivery. Advances in barrier modulation with Syn3 and vector engineering have enabled efficient delivery. Adenoviral vectors as illustrated by the FDA-approved nadofaragene firadenovec (Adstiladrin), and other platforms, such as the conditionally replicating oncolytic adenoviruses (cretostimogene, CG0070), are maturing. Combination regimens of gene therapy and immune checkpoint inhibitors have shown additive or synergistic activity, deepening durability of gene therapy. Novel advancements including urinary and plasma tumor DNA are emerging as predictive biomarkers to guide patient selection, monitor minimal residual disease, and trigger early salvage. SUMMARY: Gene-mediated therapy is gradually advancing NMIBC care, with expanding indications and potent combinations positing itself to improve bladder preservation and long-term outcomes.	bladder
Single-cell and spatial transcriptomic analysis reveal cellular heterogeneity and cancer cell-intrinsic major histocompatibility complex II expression in urothelial carcinoma.	Muscle-invasive (MI) urothelial carcinoma (UC) is a clinically challenging malignancy with a poor prognosis. Understanding the cellular dynamics that drive UC progression is critical for the development of optimized therapeutic strategies. Through integrative analysis of large-scale single-cell transcriptomic datasets from non-muscle-invasive (NMI) and MI tumours and validation with spatial transcriptomic datasets, we systematically characterized immune cell dynamics and cancer cell plasticity during UC progression. Our analysis revealed an immunosuppressive tumour microenvironment and a subset of cancer cells with upregulated major histocompatibility complex II (MHC-II) expression in MI tumours. Notably, MHC-II⁺ cancer cells were induced by interferon-γ signalling, as confirmed through in vitro experiments, and exhibited phenotypic alterations characterized by enhanced proliferative and migratory capacities. Furthermore, MHC-II⁺ cancer cells spatially colocalized with CD8⁺ T cells, regulatory T cells, and SPP1⁺ macrophages, where they engaged with inhibitory receptors on these immune cells, promoted CD8⁺ T cell exhaustion and facilitated immune evasion.	bladder
Extracellular Vesicle-Packaged MIR4435-2HG Facilitates Cigarette Smoke-Induced Bladder Cancer Progression through Enolase 1-Dependent Glycolytic Reprogramming.	Epidemiological studies have reported that cigarette smoking promotes bladder cancer progression, but the corresponding biological mechanisms must be elucidated. Cigarette smoking-related extracellular vesicle (EV)-packaged long noncoding RNAs (lncRNAs) derived from bladder tumors were identified via RNA sequencing, tissue microarrays, and single-cell RNA sequencing. The clinical value of candidate EV-packaged lncRNAs was evaluated in the urine and plasma of bladder cancer patients with smoking history. The underlying mechanism of EV-packaged lncRNAs was explored using CRISPR/Cas9, Seahorse, and N4-acetylcytidine (ac4C) acetylation experiments in vivo and in vitro. The EV-packaged lncRNA MIR4435-2HG, which was originally secreted by M2 macrophages in response to exposure to the cigarette smoking-related carcinogen 4-aminobiphenyl (4-ABP), exhibited an abundant expression pattern. Mechanistically, 4-ABP promoted M2 macrophage polarization and increased fused in sarcoma (FUS) expression by inducing signal transducer and activator of transcription 6 (STAT6) phosphorylation, contributing to the direct packaging of MIR4435-2HG into M2 macrophage-derived EVs and subsequent delivery to recipient tumor cells. The nuclear EV-packaged MIR4435-2HG subsequently bound N-acetyltransferase 10 (NAT10) and increased the stability of the glycolysis regulator Enolase 1 (ENO1) through the ac4C modification; cytoplasmic EV-packaged MIR4435-2HG sponged miR-143-3p, increased ENO1 expression, and ultimately activated PI3K-Akt signaling for glycolytic reprogramming to promote tumor development. In addition, recipient tumor cells internalized EV-packaged MIR4435-2HG and simultaneously secreted chemokines to recruit monocytes, establishing a potential feed-forward loop between M2 macrophages and tumor cells. This study identified EV-packaged MIR4435-2HG as a crucial bladder cancer marker that mediates intercellular communication during cigarette smoke exposure, suggesting a promising approach for bladder cancer prevention and treatment.	bladder
CT-based radiomics signature of visceral adipose tissue for prediction of early recurrence in patients with NMIBC: a multicentre cohort study.	INTRODUCTION: The objective of this study is to investigate the predictive ability of abdominal fat features derived from computed tomography (CT) to predict early recurrence within a year following the initial transurethral resection of bladder tumor (TURBT) in patients with non-muscle-invasive bladder cancer (NMIBC). A predictive model is constructed in combination with clinical factors to aid in the evaluation of the risk of early recurrence among patients with NMIBC after initial TURBT. METHODS: This retrospective study enrolled 325 NMIBC patients from three centers. Machine learning-based visceral adipose tissue (VAT) radiomics models (VAT-RM) and subcutaneous adipose tissue (SAT) radiomics models (SAT-RM) were constructed to identify patients with early recurrence. A combined model integrating VAT-RM and clinical factors was established. The predictive performance of each variable and model was analyzed using the area under the receiver operating characteristic curve (AUC). The net benefit of each variable and model was presented through decision curve analysis (DCA). The calibration was evaluated utilizing the Hosmer-Lemeshow test. FINDINGS: The VAT-RM demonstrated satisfactory performance in the training cohort (AUC = 0.853; 95% CI: 0.768-0.937), test cohort 1 (AUC = 0.823; 95% CI: 0.730-0.916), and test cohort 2 (AUC = 0.808; 95% CI: 0.681-0.935). Across all cohorts, the AUC values of the VAT-RM were higher than those of the SAT-RM ( P  < 0.001). The DCA curves further confirmed that the clinical net profit of the VAT-RM was superior to that of the SAT-RM. In multivariate logistic regression analysis, the VAT-RM emerged as the most significant independent predictor [odds ratio (OR) = 0.295; 95% CI: 0.141-0.508; P < 0.001]. The fusion model exhibited excellent AUC values of 0.938, 0.909, and 0.905 across three cohorts. The fusion model surpassed the traditional risk assessment frameworks in both predictive efficacy and clinical net benefit. INTERPRETATION: VAT serves as a crucial factor in early postoperative recurrence in NMIBC patients. The VAT-RM can accurately identify high-risk patients with early postoperative recurrence, offering significant advantages over SAT-RM. The new predictive model constructed by integrating the VAT-RM and clinical factors exhibits excellent predictive performance, clinical net benefits, and calibration accuracy.	bladder
MAIT cells promote cancer progression and regulatory T cell accumulation in bladder tumor microenvironment.	BACKGROUND: Mucosa-associated invariant T (MAIT) cells represent a unique population of innate-like T lymphocytes capable of detecting non-peptide antigens in the context of monomorphic antigen-presenting molecules. Due to their abundance in barrier tissues, reactivity to local inflammatory cues, and cytotoxic and regulatory functions, MAIT cells are poised to shape the dynamics of various tumor microenvironments. Growing evidence suggests that MAIT cells can exert protumor and/or antitumor effects in cancers arising from or metastasizing to mucosal tissues. However, MAIT cell roles in bladder cancer (BCa) remains unclear. METHODS: To begin to identify MAIT cells in BCa, we stained bladder tumor biopsies for T cell receptor (TCR) Vα7.2(+) cells. We then refined a human MAIT cell signature, which enabled us to interrogate a bulk RNA sequencing dataset and conduct correlation analyses linking intratumoral MAIT cell abundance and mortality from BCa. To extend our work to an in vivo setting, we employed a clinically relevant mouse model in which Mr1 (+/+) B6-MAIT(CAST) (MAIT-sufficient) and Mr1 (-/-) B6-MAIT(CAST) (MAIT-deficient) mice were exposed to N-butyl-N-(4-hydroxybutyl)nitrosamine, a chemical carcinogen associated with tobacco smoke. In additional experiments, MAIT cells were functionally removed through acetyl-6-formylpterin (Ac-6-FP) administration. Effector and regulatory cell types were phenotyped by flow cytometry, and BCa tumor burden and progression were assessed by MRI and/or H&E and Ki67 staining. RESULTS: TCR Vα7.2(+) cells were readily detectable in several BCa biopsies, and our bioinformatic analyses correlated heavier MAIT cell presence in BCa tumors with poorer overall survival. Similarly, we found higher tumor burdens in Mr1(+/+) B6-MAIT(CAST) mice than in Mr1(-/-) or Ac-6-FP-treated animals. Bladder MAIT cells from tumor-bearing mice exhibited phenotypic MAIT17 bias based on transcription factors they harbored along with increased interleukin-17A and tumor necrosis factor-α production capacities upon stimulation. Finally, FoxP3(+) regulatory T (T(reg)) cell frequencies were elevated in Mr1(+/+) mouse bladder tumors, likely contributing to an immunosuppressive tumor microenvironment, a finding that could be recapitulated in our transcriptomic studies on human BCa. CONCLUSIONS: MAIT cells are abundant in BCa tumor microenvironments where they potentiate T(reg) cell accumulation and play protumor roles.	bladder
TRIM29 promotes bladder cancer invasion by regulating the intermediate filament network and focal adhesion.	Bladder cancer is a common malignancy whose lethality is determined by invasive potential. We have previously shown that TRIM29, also known as ATDC, is transcriptionally regulated by TP63 in basal bladder cancers where it promotes invasive progression and metastasis, but the molecular events which promote invasion and metastasis downstream of TRIM29 remained poorly understood. Here we identify stimulation of bladder cancer migration as the specific role of TRIM29 during invasion. We show that TRIM29 physically interacts with K14+ intermediate filaments which, in turn, regulates focal adhesion stability. Further, we find that both K14 and the focal adhesion protein, ZYX are required for bladder cancer migration and invasion. Taken together, these results establish a role for TRIM29 in the regulation of cytoskeleton and focal adhesions during invasion and identify a pathway with therapeutic potential.	bladder
Evaluating diagnostic performance of urinary biomarkers in the surveillance of non-muscle invasive bladder carcinoma: A systematic review.	PURPOSE: Urinary biomarkers have been proposed to play an integral role in detecting recurrent non-muscle invasive bladder carcinoma (NMIBC). This review delineates the diagnostic accuracy of such biomarkers and management strategies in the event of discordance between biomarker findings and flexible cystoscopy, the current gold standard for NMIBC surveillance. MATERIALS AND METHODS: In accordance with the PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) statement, literature searches were conducted across PubMed, Embase, Scopus, and CENTRAL (Cochrane Central Register of Controlled Trials), focusing on studies comparing urinary biomarkers to cystoscopy. The inclusion criteria were based on the PICOS (Patient Intervention Comparison Outcome Study type) model. The quality of included studies was assessed using the QUADAS-2 tool. RESULTS: A total of 23 studies were included, encompassing 21 types of urinary biomarkers. The analysis revealed significant variability in diagnostic performance. Sensitivity ranged from 14.8% to 94.3%, specificity from 33.3% to 99.2%, positive predictive value from 9.9% to 100%, and negative predictive value from 35.3% to 98.8%. Heterogeneity was observed across studies, indicating variability in different biomarker performance. Genetic biomarkers demonstrated higher diagnostic accuracy compared to protein-based markers. However, their clinical utility needs further validation. CONCLUSIONS: Urinary biomarkers could complement, rather than replace cystoscopy, in the surveillance of NMIBC, potentially reducing the frequency of invasive procedures. In cases of discordance, an algorithm focusing on shared decision-making and tailored surveillance strategies can be undertaken. Large-scale multicentric studies are needed to confirm their efficacy and establish standardized clinical protocols.	bladder
Bladder cancer immunotherapy parallel advances in BCG optimization and next-generation vaccine platforms.	Bladder cancer (BCa) remains a significant global health challenge with rising incidence and suboptimal outcomes in advanced stages. Although immunotherapy for urological cancers is not a new treatment, recent clinical advances have confirmed the value of immunotherapy as a urological cancer treatment. In the field of cancer immunotherapy, increasing attention has been focused on the use of cancer vaccines that activate T cells to target growing tumors. Despite Bacillus Calmette-Guérin (BCG) intravesical immunotherapy serving as the first-line treatment for non-muscle-invasive bladder cancer (NMIBC), its limitations, including systemic toxicity, BCG unresponsiveness, and rapid bladder clearance-necessitate novel therapeutic strategies. This descriptive review synthesizes recent advances in BCG optimization and emerging cancer vaccines for BCa, including peptides, antigen-presenting cells, viruses, or nucleic acids, that seeks to stimulate the patient's immune response targeting tumor cells. Our study underscores the transformative potential of next-generation vaccines in redefining BCa management while addressing critical barriers to implementation.	bladder
AI-informed computational pathology classifier predicts outcomes across treatment modalities in muscle-invasive urothelial carcinoma.	Urothelial carcinoma (UC) is one of the leading causes of cancer-related mortality, and effective, scalable biomarkers for treatment planning remain limited. We present UC-TIL, an artificial intelligence (AI)-based model that quantifies spatial patterns of tumor-infiltrating lymphocytes (TILs) from routine H&E-stained slides to predict survival and immunotherapy response. We analyzed 558 whole-slide images across three cohorts: TCGA (D(0)&(1), N = 292), Emory (D(2), N = 161), and TRRC2819 (D(3), N = 105), spanning chemotherapy and immune checkpoint inhibitor (ICI) treatments. UC-TIL classification was associated with OS (HR = 2.11, 95 %CI:1.01-4.41, p = 0.011) and PFS (HR = 3.68, 95 %CI:1.07-12.65, p = 0.0012) in locally advanced disease (D(1) and D(2)), with consistent results in metastatic disease (D(3)) (HR = 1.73, 95 %CI:1.08-2.77, p = 0.043; PFS HR = 1.73, 95 %CI:1.07-2.81, p = 0.047). In the ICI-treated D(3) cohort, UC-TIL achieved AUC = 0.757 and identified non-responders with 91 % specificity. UC-TIL enables reliable risk stratification and treatment response prediction in both locally advanced and metastatic urothelial carcinoma by analyzing spatial TIL patterns from standard pathology slides. These findings position UC-TIL as a readily deployable tool to guide personalized therapy across multiple clinical settings.	bladder
Enfortumab Vedotin-Related Skin Toxicities: Insights From Clinical and Histopathological Analysis.	Enfortumab vedotin (EV), targeting Nectin-4, is effective in advanced urothelial carcinoma but frequently causes skin toxicities. This study examined the possible contribution of prior immune checkpoint inhibitor (ICI) therapy and higher EV doses to EV-related skin toxicity (EVST) development. Histopathological findings suggested both direct keratinocyte damage and immune-mediated mechanisms. These insights may improve clinical management of EVST.	bladder
Neutrophil extracellular traps-STC1 positive feedback loop promotes immune evasion and metastasis in bladder cancer.	BACKGROUND: Immune checkpoint inhibitors (ICIs) have transformed the treatment strategy for bladder cancer (BLCA), but primary resistance still occurs in most patients. Recent evidence suggests that neutrophil extracellular traps (NETs) play a key role in cancer therapy resistance, but their specific role in BLCA remains unclear. METHODS: An integrated analysis of multiple clinical cohorts receiving ICIs was performed to explore the link between NETs and patient outcomes. Immunofluorescence staining, in vitro co-culture system, scanning electron microscopy, and mouse lung metastasis model were used to evaluate the biological effects of NETs. Proteomics and single-cell transcriptomics analysis were further applied to elucidate the molecular mechanisms. RESULTS: Clinically, NETs abnormally accumulated in BLCA and promoted tumor metastasis and immunotherapy resistance in mice. Mechanistically, NETs upregulated the anti-phagocytic checkpoint STC1 in tumor cells through the TLR2-MAPK-FosL1 axis. Notably, STC1 inhibited antigen presentation by sequestering calreticulin, while its secreted form enhances NET formation, forming a self-reinforcing feedback loop. In addition, secreted STC1 impaired differentiation of CD14(+) precursors into mature dendritic cells, further exacerbating immune suppression. CONCLUSION: This study revealed the critical role of the NETs-STC1 feedback loop in BLCA immunoresistance. Targeting this axis could simultaneously enhance efficacy and safety of immunotherapy, providing a novel translational strategy for overcoming resistance in clinical settings.	bladder
Treatment strategies for cisplatin-ineligible metastatic bladder cancer: Emerging therapies and future perspectives.	Recently, the combination of enfortumab vedotin and pembrolizumab has been recommended as the preferred first-line therapy for metastatic or locally advanced urothelial carcinoma owing to its substantial survival benefits. However, its high-cost limits accessibility, leading to many patients receiving cisplatin-based chemotherapy as a more practical alternative. Therefore, cisplatin-based combination chemotherapy remains a widely used first-line treatment for metastatic bladder cancer (MBC). Nonetheless, nearly half of the patients are ineligible for cisplatin owing to factors such as renal impairment, poor performance status, or other comorbidities. The definition of cisplatin ineligibility, which is often based on the Galsky criteria, lacks robust scientific validation, and limited pharmacokinetic data on the effects of cisplatin in patients with renal impairment are available. This review explored alternative treatment strategies for cisplatin-ineligible patients, including immune checkpoint inhibitors, carboplatin-based regimens, antibody-drug conjugates, and novel combination therapies. Notably, recent advancements, such as the combination of enfortumab vedotin and pembrolizumab, have shown promising survival benefits in this patient population. Additionally, emerging targeted therapies, such as fibroblast growth factor receptor inhibitors, are reshaping the treatment landscape of cisplatin-ineligible patients with MBC, emphasizing the need for personalized approaches that balance efficacy and safety.	bladder
Aberrant KIF26B expression promotes bladder cancer progression through driving NSUN2 nuclear localization.	Abnormal expression of kinesins has been observed in several types of cancer. The present study provided the first evidence that KIF26B could induce RNA m(5)C modification in bladder cancer (BCa). Detailly, KIF26B interacted with NSUN2 and recruited ubiquitinase STUB1 to promote K63-linked ubiquitination of NSUN2 at K511 site. K63-linked ubiquitination enabled NSUN2 to bind to KPNA1 and translocate into nucleus where it drove RNA m(5)C modification. Furthermore, KIF26B induced liquid-liquid phase separation (LLPS) of YBX1 and upregulated IL-6 expression through NSUN2/m(5)C/YBX1 axis. Secreted IL-6 then activated STAT3 signaling to promote transcription of kif26b through direct binding between STAT3 and kif26b promoter. IL-6 also recruited DLAT to acetylate NSUN2 at K229 site and increased association affinity between NSUN2 and KIF26B. Together, these established a KIF26B/NSUN2/m(5)C/IL-6 positive feedback loop, suggesting that targeting KIF26B may be a promising therapeutic strategy for BCa.	bladder
Mechanisms, Clinical Trials, and New Treatments for BCG-Unresponsive in Nonmuscle Invasive Bladder Cancer.	BACKGROUND: Bacillus Calmette-Guérin (BCG) is the standard adjuvant therapy for high-risk non-muscle invasive bladder cancer (NMIBC), yet treatment failure occurs in 30% to 40% of patients. Those with BCG-unresponsive disease face a high risk of progression and represent a critical unmet need in urologic oncology. This review summarizes the mechanisms of BCG failure and evaluates emerging therapies for BCG-unresponsive NMIBC. METHODS: We conducted a comprehensive literature review of clinical trials and preclinical studies through August 2025, focusing on therapeutic strategies for BCG-unresponsive NMIBC. Mechanisms of BCG resistance, regulatory definitions, and results from recent Phase II/III trials were analyzed. RESULTS: Multiple novel therapies have demonstrated efficacy in BCG-unresponsive patients. Immune checkpoint inhibitors (e.g., pembrolizumab) achieved complete response (CR) rates of 41% in carcinoma in situ (CIS) patients. Gene therapies such as nadofaragene firadenovec and CG0070 induced CR rates of 51% and 75%, respectively. Device-assisted therapies including hyperthermic intravesical chemotherapy (HIVEC) showed 24-month recurrence-free survival of 57.4%. The IL-15 superagonist Anktiva (nogapendekin alfa inbakicept), recently FDA-approved, achieved a 71% CR rate with a median duration of 26.6 months when combined with BCG. CONCLUSIONS: The treatment landscape for BCG-unresponsive NMIBC is rapidly evolving, with immune checkpoint inhibitors, gene therapies, targeted agents, and advanced drug delivery systems showing promising efficacy. These innovations provide bladder-preserving options for patients ineligible for radical cystectomy. Future directions include biomarker-driven therapy selection, combination regimens, and optimized intravesical delivery platforms to improve long-term outcomes.	bladder